Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, P.R. China.
Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, P.R. China.
J Nutr Biochem. 2023 Sep;119:109402. doi: 10.1016/j.jnutbio.2023.109402. Epub 2023 Jun 11.
Non-alcoholic fatty liver disease (NAFLD), is the most common cause of chronic liver disease, affecting 24% of the global population. Accumulating evidence demonstrates that copper deficiency (CuD) is implicated in the development of NAFLD, besides, high fructose consumption by promoting inflammation contributes to NAFLD. However, how CuD and/or fructose (Fru) causes NAFLD is not clearly delineated. The present study aims to investigate the role of CuD and/or fructose supplement on hepatic steatosis and hepatic injury. We established a CuD rat model by feeding weaning male Sprague-Dawley rats for 4 weeks with CuD diet. Fructose was supplemented in drinking water. We found the promoting role of CuD or Fructose (Fru) in the progress of NAFLD, which was aggravated by combination of the two. Furthermore, we presented the alteration of hepatic lipid profiles (including content, composition, and saturation), especially ceramide (Cer), cardiolipin (CL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was closely associated with CuD and/or Fru fed induced-NAFLD in rat models. In conclusion, insufficient copper intake or excessive fructose supplement resulted in adverse effects on the hepatic lipid profile, and fructose supplement causes a further hepatic injury in CuD-induced NAFLD, which illuminated a better understanding of NAFLD.
非酒精性脂肪性肝病 (NAFLD) 是最常见的慢性肝病病因，影响全球 24%的人口。越来越多的证据表明，铜缺乏 (CuD) 与 NAFLD 的发展有关，此外，高果糖的摄入通过促进炎症也有助于 NAFLD 的发生。然而，CuD 和/或果糖 (Fru) 如何导致 NAFLD 尚不清楚。本研究旨在探讨 CuD 和/或果糖补充对肝脂肪变性和肝损伤的作用。我们通过用 CuD 饮食喂养断奶雄性 Sprague-Dawley 大鼠 4 周来建立 CuD 大鼠模型。果糖补充在饮用水中。我们发现 CuD 或 Fru 在 NAFLD 进展中的促进作用，两者结合后加重了这种作用。此外，我们还提出了肝脂质谱（包括含量、组成和饱和度）的改变，特别是神经酰胺 (Cer)、心磷脂 (CL)、磷脂酰胆碱 (PC) 和磷脂酰乙醇胺 (PE) 与 CuD 和/或 Fru 喂养诱导的大鼠模型中的 NAFLD 密切相关。总之，铜摄入不足或果糖补充过量对肝脂质谱有不良影响，而果糖补充在 CuD 诱导的 NAFLD 中进一步导致肝损伤，这阐明了对 NAFLD 的更好理解。
